Verapamil, a calcium channel antagonist, has been evaluated in schizophrenia. We have demonstrated partitioning of the drug and its active metabolites into the CSF for the first time by using a sensitive and specific method. Further analysis of data with the biochemical response measures indicated that verapamil causes significant worsening of hostile and uncooperative behaviors. Also a significant increase was observed in the plasma HVA during verapamil treatment periods. Plasma levels of prolactin were also increased from baseline or placebo. Changes in plasma HVA correlated with the change in the levels of MHPG (3-methoxy 4-hydroxyphenethyleneglycol) (r=-0.74,p=0.06). CSF verapamil levels are significantly related to plasma verapamil levels (r=0.85) but not to plasma norverapamil. CSF metabolite levels correlated with plasma levels of metabolites also. Verapamil does not appear to exert any beneficial effect in schizophrenics as it does in manics. We have also determined the protein and glycoprotein binding of verapamil in patients to understand its partitioning across membranes.